Tissue engineering faces several challenges in the development of replacement tissue. First, the “replaced” tissue must promote tissue regeneration. In doing so, the replaced tissue must be compatible with the tissue it is replacing so that neighboring cells accept the replacement and do not disrupt tissue continuity. Importantly, the replaced tissue also has to overcome the immunologic challenges faced by any new addition to a biologic system, that of a “foreign body.” Furthermore, to be successful, the replaced tissue must eventually exhibit the properties and function of tissue that it is replacing. For example, the replaced tissue should exhibit similar mechanical and structural properties of the native environment or at a minimum, not interfere with the native environment. The replaced tissue may also act as a scaffold to promote cellular regeneration. Finally, the replaced tissue should not stimulate scar formation that limits tissue regeneration or inhibits the natural function of the underlying tissue.
Strategies for successful regeneration include the use of biologic or biocompatible materials to build a bridge across the injured area. While successful for some tissue, many biomaterials have been rejected or have promoted regional “scarring.” In addition, the mechanical and structural differences that define the function of different types of tissue have proven difficult to overcome, especially for tissue such as nerves.
These same strategies are modeled on the fabrication of synthetic or biocompatible tissue in vitro that is representative of a native tissue. One example is the use of vascular grafts using an acellular tubular structure that is then implanted at the injured site. The grafts will eventually be invaded by normal cells and the tubular structure will remain viable over time. While promising for tissue with limited needs for mobility, these biocompatible structures are generally stiffer than the surrounding tissue and uncompromising in areas requiring flexibility. Alternatively, biodegradable scaffolds have been engineered with the hope that, over time, the degradable component(s) will be replaced by constituents that make up the normal tissue and will exert the same function as performed by the original tissue. The biodegradable scaffold strategy has seen limited success except to accelerate otherwise naturally occurring phenomena, and have not successfully replaced tissue with high structural or mobility requirements (e.g., bone, nerve, muscle).
For some tissue (e.g. nerve tissue), several other techniques have been used to try to initiate tissue regeneration. For example, acute administration of hydrophilic polymer or polymer blends is used to seal nerve membranes. The polymer application may reconnect or fuse severed axons of damaged nerve membranes and may even promote recovery of excitability in some damaged nerve fibers. However, large injuries are ineffectively repaired using this method, where tension has been found to limit regeneration.
Peripheral nerve allografts have shown some promising success, generally, in the presence of one or more immunosuppressive agents to reduce nerve rejection. The popularity of using nerve conduits for tissue regeneration has increased recently due to the need for alternative tissue reconstruction techniques that yield fewer complications and greater mobility for the individual. In fact, active regenerating fibers on a proximal stump of a nerve have been found to regenerate and progress as a fascicular unit in optimum condition at the trunk of another healthy nerve.
There remains a need to improve tissue replacements, especially for tissue such as nerve that has proven difficult to regenerate with current tissue replacement strategies. The improved tissue replacement should maintain native characteristics of the tissue it is replacing, be able to incorporate bioactive compounds or molecules where necessary to promote rapid regeneration, and stimulate tissue repair and regeneration in the absence of tissue scarring that reduces tissue mobility and integrity. Despite current research efforts in tissue regeneration, there still exists a need for a clinically attractive alternative to autografts.